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首页> 外文期刊>RSC Advances >Targeted delivery of bromelain using dual mode nanoparticles: synthesis, physicochemical characterization, in vitro and in vivo evaluation
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Targeted delivery of bromelain using dual mode nanoparticles: synthesis, physicochemical characterization, in vitro and in vivo evaluation

机译：双模式纳米粒子靶向菠萝蛋白酶的靶向递送：合成，理化特性，体外和体内评估

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The engineering, characterization, and application of dual-functional delivery vehicle “SPIONs–Br–FA” are reported. In this study, a citrate-coated SPIONs (superparamagnetic iron oxide nanoparticles) drug-delivery vehicle was conjugated with Br (bromelain), a phytotherapeutic anticancer agent, and finally immobilized with FA (folic acid), as a targeting moiety to the FAR+, folate receptor positive, cancer cells. Then, in vitro compatibility tests were performed to confirm the biocompatibility of the engineered system. A cytotoxicity study was carried out, which showed a significant dose advantage with SPIONs–Br–FA in reducing the IC50 values of FAR+ cancer cells compared with neat Br. Through morphological alternation studies, it was disclosed that the SPIONs–Br–FA-treated cells had undergone apoptosis, since shrinkage as well as apoptotic bodies were obviously observed. We demonstrated that SPIONs–Br–FA was a good candidate to suppress the migration of the FAR+ cancer cells as well as to inhibit colony formation of the FAR+ cancer cells compared to SPIONs–Br. We found that the apoptosis percentage was sharply increased in the FAR+ cancer cells treated by SPIONs–Br–FA compared to those treated by neat Br. Moreover, the qualitative and quantitative biodistribution study performed on the vital organs and tumor indicated a significant tumor targetability of the SPIONs–FA. Next, we demonstrated the administration of SPIONs–Br–FA through the tail vein could reduce the tumor burden in 4T1-bearing mice and also increased their lifespan when compared with SPIONs–Br and neat Br at the same concentration of bromelain. In conclusion, the results indicated that the synthesized SPIONs–Br–FA is a promising tool in the field of biomedicine, particularly in cancer therapy.
机译：报告了双功能运载工具“ SPIONs–Br–FA”的工程，特性和应用。在这项研究中，将柠檬酸盐涂层的SPIONs（超顺磁性氧化铁纳米颗粒）药物递送载体与植物治疗性抗癌药Br（溴阿米林）偶联，最后固定为FAR +的靶向部分FA（叶酸），叶酸受体阳性，癌细胞。然后，进行了体外相容性测试，以确认工程系统的生物相容性。进行了细胞毒性研究，结果表明，与纯Br相比，SPIONs–Br–FA在降低FAR +癌细胞的IC 50 值方面具有显着的剂量优势。通过形态学交替研究，发现经SPIONs-Br-FA处理的细胞已发生凋亡，因为明显观察到了收缩和凋亡小体。我们证明，与SPIONs-Br相比，SPIONs-Br-FA是抑制FAR +癌细胞迁移以及抑制FAR +癌细胞集落形成的良好候选者。我们发现，用SPIONs–Br–FA处理的FAR +癌细胞的凋亡百分比与未使用纯Br处理的癌细胞的凋亡百分比急剧增加。此外，对重要器官和肿瘤的定性和定量生物分布研究表明，SPIONs-FA具有显着的肿瘤靶向性。接下来，我们证明了在相同的菠萝蛋白酶浓度下，与SPIONs-Br和纯Br相比，通过尾静脉施用SPIONs-Br-FA可以减轻带有4T1的小鼠的肿瘤负担，并可以延长它们的寿命。总之，结果表明，合成的SPIONs-Br-FA在生物医学领域，特别是在癌症治疗领域是有前途的工具。

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